Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry a...Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis.Cellular ultrastructure was observed by transmission electron microscopy.The levels of p-mixed lineage kinase domain-like(MLKL),gasdermin-D(GSDMD),gasdermin E(GSDME),N-GSDMD,and N-GSDME proteins were detected by Western blotting.In addition,lactate dehydrogenase(LDH)release assay was used to verify pyroptosis induced by chaetocin,and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms.Results:Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS,HGC27,MKN28,and SGC7901gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis.Significant ultrastructure changes,such as chromatin condensation,vacuolization,disrupted mitochondrial cristae,and increased nuclear occupancy,were observed after treatment with chaetocin in SGC7901 cells.Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells,LDH release,and the ratio of N-GSDME/GSDME(P<0.01),which were reversed by Z-DEVD-FMK.In addition,chaetocin did not affect the expression of GSDMD.G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release(P>0.05).Conclusions:In addition to inducing apoptosis,chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway.G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.展开更多
Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated...Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo.Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression,inducing cancer cell apoptosis(intrinsic and extrinsic),enhancing autophagy,inducing cell cycle arrest,as well as inhibiting tumour angiogenesis,invasion and migration.The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper,and the prospective applications of chaetocin in cancer prevention and therapy are also discussed.Our review provides the theoretical basis for exploiting the clinical application of chaetocin in cancer treatment.展开更多
Oxidative stress,regarded as a negative effect of free radicals in vivo,takes place when organisms suffer from harmful stimuli.Some viruses can induce the release of reactive oxygen species(ROS) in infected cells,whic...Oxidative stress,regarded as a negative effect of free radicals in vivo,takes place when organisms suffer from harmful stimuli.Some viruses can induce the release of reactive oxygen species(ROS) in infected cells,which may be closely related with their pathogenicity.In this report,chaetocin,a fungal metabolite reported to have antimicrobial and cytostatic activity,was studied for its effect on the activation of latent Epstein-Barr virus(EBV) in B95-8 cells.We found that chaetocin remarkably up-regulated EB V lytic transcription and DNA replication at a low concentration(50 nmol L^(-1).The activation of latent EBV was accompanied by an increased cellular ROS level.N-acetyl-L-cy steine(NAC),an ROS inhibitor,suppressed chaetocin-induced EBV activation.Chaetocin had little effect on histone H3K9 methylation,while NAC also significantly reduced H3K9 methylation.These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.展开更多
基金supported by Natural Science Foundation of Hainan Province,China(No.820MS048)。
文摘Objective:To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms.Methods:The proliferation of gastric cancer cells was detected by trypan blue staining.Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis.Cellular ultrastructure was observed by transmission electron microscopy.The levels of p-mixed lineage kinase domain-like(MLKL),gasdermin-D(GSDMD),gasdermin E(GSDME),N-GSDMD,and N-GSDME proteins were detected by Western blotting.In addition,lactate dehydrogenase(LDH)release assay was used to verify pyroptosis induced by chaetocin,and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms.Results:Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS,HGC27,MKN28,and SGC7901gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis.Significant ultrastructure changes,such as chromatin condensation,vacuolization,disrupted mitochondrial cristae,and increased nuclear occupancy,were observed after treatment with chaetocin in SGC7901 cells.Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells,LDH release,and the ratio of N-GSDME/GSDME(P<0.01),which were reversed by Z-DEVD-FMK.In addition,chaetocin did not affect the expression of GSDMD.G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release(P>0.05).Conclusions:In addition to inducing apoptosis,chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway.G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.
文摘Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo.Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression,inducing cancer cell apoptosis(intrinsic and extrinsic),enhancing autophagy,inducing cell cycle arrest,as well as inhibiting tumour angiogenesis,invasion and migration.The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper,and the prospective applications of chaetocin in cancer prevention and therapy are also discussed.Our review provides the theoretical basis for exploiting the clinical application of chaetocin in cancer treatment.
文摘Oxidative stress,regarded as a negative effect of free radicals in vivo,takes place when organisms suffer from harmful stimuli.Some viruses can induce the release of reactive oxygen species(ROS) in infected cells,which may be closely related with their pathogenicity.In this report,chaetocin,a fungal metabolite reported to have antimicrobial and cytostatic activity,was studied for its effect on the activation of latent Epstein-Barr virus(EBV) in B95-8 cells.We found that chaetocin remarkably up-regulated EB V lytic transcription and DNA replication at a low concentration(50 nmol L^(-1).The activation of latent EBV was accompanied by an increased cellular ROS level.N-acetyl-L-cy steine(NAC),an ROS inhibitor,suppressed chaetocin-induced EBV activation.Chaetocin had little effect on histone H3K9 methylation,while NAC also significantly reduced H3K9 methylation.These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.
